{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:06:21Z","timestamp":1790712381175,"version":"4.1.0"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2014,5,22]]},"abstract":"\n Background<\/jats:title>\n \n Cerebral arteriovenous malformation (\n AVM<\/jats:styled-content>\n ) is a vascular disease exhibiting abnormal blood vessel morphology and function. miR\u201018a ameliorates the abnormal characteristics of\n AVM<\/jats:styled-content>\n \u2010derived brain endothelial cells (\n AVM<\/jats:styled-content>\n \u2010\n BEC<\/jats:styled-content>\n ) without the use of transfection reagents. Hence, our aim was to identify the mechanisms by which miR\u201018a is internalized by\n AVM<\/jats:styled-content>\n \u2010\n BEC<\/jats:styled-content>\n . Since\n AVM<\/jats:styled-content>\n \u2010\n BEC<\/jats:styled-content>\n overexpress\n RNA<\/jats:styled-content>\n \u2010binding protein Argonaute\u20102 (Ago\u20102) we explored the clinical potential of Ago\u20102 as a systemic mi\n RNA<\/jats:styled-content>\n carrier.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Primary cultures of\n AVM<\/jats:styled-content>\n \u2010\n BEC<\/jats:styled-content>\n were isolated from surgical specimens and tested for endogenous miR\u201018a levels using\n qPCR<\/jats:styled-content>\n . Conditioned media (\n CM<\/jats:styled-content>\n ) was derived from\n AVM<\/jats:styled-content>\n \u2010\n BEC<\/jats:styled-content>\n cultures (\n AVM<\/jats:styled-content>\n \u2010\n BEC<\/jats:styled-content>\n \u2010\n CM<\/jats:styled-content>\n ).\n AVM<\/jats:styled-content>\n \u2010\n BEC<\/jats:styled-content>\n \u2010\n CM<\/jats:styled-content>\n significantly enhanced miR\u201018a internalization. Ago\u20102 was detected using western blotting and immunostaining techniques. Ago\u20102 was highly expressed in\n AVM<\/jats:styled-content>\n \u2010\n BEC<\/jats:styled-content>\n ; and siAgo\u20102 decreased miR\u201018a entry into brain\u2010derived endothelial cells. Only brain\u2010derived endothelial cells were responsive to the Ago\u20102\/miR\u201018a complex and not other cell types tested. Secreted products (eg, thrombospondin\u20101 [TSP\u20101]) were tested using ELISA. Brain endothelial cells treated with the Ago\u20102\/miR\u201018a complex in vitro increased TSP\u20101 secretion. In the in vivo angiogenesis glioma model, animals were treated with miR\u201018a in combination with Ago\u20102. Plasma was obtained and tested for TSP\u20101 and vascular endothelial growth factor (VEGF)\u2010A. In this angiogenesis model, the Ago\u20102\/miR\u201018a complex caused a significant increase in TSP\u20101 and decrease in VEGF\u2010A secretion in the plasma.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Ago\u20102 facilitates miR\u201018a entry into brain endothelial cells in vitro and in vivo. This study highlights the clinical potential of Ago\u20102 as a mi\n RNA<\/jats:styled-content>\n delivery platform for the treatment of brain vascular diseases.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.114.000968","type":"journal-article","created":{"date-parts":[[2014,5,17]],"date-time":"2014-05-17T07:47:56Z","timestamp":1400312876000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":33,"title":["Argonaute\u20102 Promotes miR\u201018a Entry in Human Brain Endothelial Cells"],"prefix":"10.1161","volume":"3","author":[{"given":"Raquel","family":"Ferreira","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiago","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Amar","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas C.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA"},{"name":"Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley M.","family":"Tahara","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven L.","family":"Giannotta","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence M.","family":"Hofman","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA"},{"name":"Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, 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